We established that cells from Ewing tumors form neurites in response to Wnt-3a and have begun to define the mechanisms that account for this effect. Knockdown of the atypical PKCiota also blocked Wnt-3a-dependent neurite outgrowth. Wnt-3a stimulated the phosphorylation of PKCi. Dvl2 co-immunoprecipitated with PKCi, and this interaction did not occur when CK1 phosphorylation sites in Dvl2 were replaced with alanine residues. These results suggested that Dvl2 phosphorylation by CK1 was required for Dvl2-PKCi binding, which in turn might be necessary for neurite outgrowth. This work is significant not only because it provides insights about mechanisms involved in the formation of neurites. Many of the factors that participate in neurite outgrowth contribute to cell polarity in other contexts such as the formation of cellular extensions critical for cell migration. Inhibition of CK1d blocked primary ciliogenesis in hTERT-RPE and mIMCD3 cells. Mouse embryonic fibroblasts and retinal cells from CK1d null mice also exhibited ciliogenesis defects. Interference with CK1d expression or catalytic activity disrupted the pericentrosomal or ciliary distribution of several proteins involved in ciliary transport, including Rab11a, Rab8a, CEP290, PCM1 and polycystin-2, as well as the Golgi distribution of AKAP450. Similar to its binding partner AKAP450, CK1d was required for microtubule nucleation at the Golgi and maintenance of Golgi integrity. Overexpression of an AKAP450 fragment containing the CK1d binding site inhibited Golgi-derived microtubule nucleation, Golgi distribution of IFT20 and ciliogenesis. Our results suggest that CK1d mediates primary ciliogenesis by coordinating the distribution and presumably function of multiple factors at or near the centrosome and Golgi to promote ciliary transport. Defective primary cilia are responsible for several disorders including neural tube defects, polycystic kidney disease and situs inversus. Aberrant Wnt signaling also can elicit these abnormalities. Thus, our studies of CK1d and Dvl may provide new insight about the ways in which Wnt signaling controls embryonic development and its dysregulation contributes to pathogenesis.